Purpose :
Rhegmatogenous retinal detachment (RD) may cause the photoreceptor degeneration and irreversible visual loss. Previous studies reported the correlation between elevated matrix metalloproteinase (MMP) and endoplasmic reticulum (ER) stress in photoreceptor degeneration. This study is to investigate the role of MMP, ER stress and zinc homeostasis, in the patho-mechanism of RD-related photoreceptor degeneration.

Methods :
RD mice model was created by injecting 2 µl of balanced salt solution (BSS) through self-sealing scleral incision. Pathological endpoints examined in vivo included photoreceptor cell death and MMP2, MMP9, and zinc level in RD mice. In addition, the induction of ER stress and unfolded protein response (UPR) were assessed in RD mice and changes of ER stress after modulation of MMP were examined.

Results :
Photoreceptor cell death was peaked on 3 day and then dropped down. MMP 2 and MMP 9 were elevated by two-fold in RD mice eyes compared to control eyes (P < 0.05). The expressions of ER stress markers, GRP78, pPERK, and peIF2α were increased in RD mice. When MMP activator, 4-aminophenylmercuric acetate (APMA) 10 µM was treated into the subretinal space, retina remained to be detached longer and photoreceptor cell death was more increased compared to APMA untreated RD eyes. When MMP inhibitor, GM6001 1 mM was treated, on the other hands, MMP2, MMP9, and ER stress markers were decreased significantly. Regarding the level of zinc, total amount of zinc were decreased significantly in RD mice eyes (192.5 ± 12.4 µg/dl) compared to those in control fellow eyes (227.9 ± 9.6 µg/dl, P < 0.05). When chelating extracellular zinc of subretinal space with CaEDTA 100 µM, TUNEL positive photoreceptor cell were decreased.

Conclusions :
RD model induced zinc release from retina to subretinal space and it was correlated with increased MMP activation and ER stress expression. This suggests that modulating MMP and ER stress may alleviate photoreceptor cell death in RD.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.